90 Induction of Rheumatoid Factor by Immune Complexes

Several observations suggest that the Fc-specific anti-IgG autoantibodies, which were first discovered in the serum of rheumatoid patients (1, 2) and are therefore commonly called rheumatoid factors (RF), ~ may represent normal components of the immune system. RF are often detected, al though usually in low titers, in the serum of normal individuals (3), and RF-like material has been found in healthy animals o f various species, including hyper immune rabbits and unmanipulated normal mouse strains (4-7). The existence of a "normal" RF synthesis thus seems well established, but the origin and the biological significance of this phenomenon remain largely unexplained. The production of RF is considerably enhanced during active immunization against a wide variety of antigens. In humans, the frequency of RF precursor cells was found to increase after vaccination of normal adults with tetanus toxoid (8) and, in the mouse, it was observed that anamnestic immune responses to protein antigens invariably started with the production of considerable amounts of RF (9, 10). In addition, in the mouse model, it was shown that exposure to antigen initiated RF synthesis in primed animals only, which implied that the activation of RF precursor cells required some kind of interaction between antigen and primed lymphocytes and /o r immune serum components. Support for this hypothesis was obtained in adoptive transfer experiments, which demonstrated that both primed lymphocytes and immune serum were involved in the process of RF production (11). We have examined these humoral and cellular mechanisms of RF induction in greater detail.